Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis to mountain cedar.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.     

The reduction of rhinitis symptoms by nasal filters during natural exposure to ragweed and grass pollen

BACKGROUND: Prototype nasal filters were developed to collect inhaled pollen. This study evaluated the efficacy of the filters for prevention of rhinitis symptoms during acute outdoor pollen exposure. METHODS: A randomized double-blind design was used. Subjects (n=46) with a history of autumn exacerbation of rhinitis and positive skin test to ragweed, Bermuda and/or Bahia grass wore either active or placebo nasal filters for 2 h in autumn in a park containing these species. Major and Total Symptoms scores were recorded at 0, 30, 60, 90 and 120 min. RESULTS: Subjects wearing active nasal filters had significantly reduced scores, at all time-points compared with placebo group (all P <0.05). Of 14 individual symptoms measured, seven were significantly reduced (number of sneezes, runny nose, itchy nose, sniffles, itchy throat; itchy eyes and watery eyes) and another three showed a trend towards lower severity. The nasal filters also enabled the resolution of existing symptoms. Maximal difference in symptoms was seen immediately after subjects had spent 20 min sitting beside a large patch of ragweed. CONCLUSION: This is the first clinical trial of a nasal filter. The results suggest it has potential for enhancing rhinitis management during acute allergen exposure.     

A double-blind comparison of nasal budesonide and oral astemizole for the treatment of perennial rhinitis

Sixty-nine outpatients with symptomatic perennial rhinitis were recruited to this double-blind, parallel-group study to compare budesonide nasal spray with oral astemizole. Following a 1-week run-in on placebo, 67 patients achieved a mean daily total symptom score of at least 4 (scoring for each symptom was 0 = none, 1 = mild, 2 = moderate, 3 = severe), and were randomized to study treatments - 33 to budesonide, 100 ug in each nostril morning and evening, and 34 to astemizole, one 10-mg tablet each morning, for a period of 4 weeks. No antihistamine preparations other than eye drops and no corticosteroids were permitted during the active treatment period. Patients recorded symptoms of blocked nose, runny nose, sneezing, itchy nose, sore eyes or runny eyes in diary cards each evening before retiring. Diary card data showed that there was significantly greater improvement in blocked nose, runny nose and runny eyes during the first 2 weeks of budesonide treatment than during the same period on astemizole. A similar, although non-significant, trend was observed for sneezing and itchy nose, but there was no apparent difference in the reporting of sore eyes. After 4 weeks, blocked nose and runny nose remained significantly less troublesome in the budesonide group. Both treatments were well-tolerated and no major adverse effects were reported. Patient ratings for treatment efficacy were significantly higher for budesonide than astemizole at both 2 weeks and 4 weeks.     

Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis

BACKGROUND: The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T (Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc. RESULTS: Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 microg) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002). CONCLUSIONS: Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.     

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo in patients with SAR. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 565 patients aged 12 to 80 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms and completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Olopatadine spray (0.4% and 0.6%) was significantly superior to placebo for percentage change from baseline in overall reflective (P = .004 and P < .001, respectively) and instantaneous (P = .02 and P = .003, respectively) TNSSs. Also, 0.6% olopatadine was significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny and itchy nose, and itchy eyes; the instantaneous assessments of watery eyes; and the overall and all 7 domain scores of the RQLQ (P < .05). Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs (reflective and instantaneous) and in quality-of-life variables in patients with SAR. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.     

Allergy immunotherapy tablet: Grazax® for the treatment of grass pollen allergy

Immunotherapy is the only treatment for allergy that alters the natural course of this disease. Sublingual immunotherapy has been developed to make immunotherapy more suitable for allergic patients. In the largest clinical program ever conducted with grass allergen-specific immunotherapy, over 2000 adults and more than 500 children have been exposed to Grazax(?) (ALK-Abello A/S, Hoersholm, Denmark). Grazax is an oral lyophilisate tablet (allergy immunotherapy tablet [AIT]) for sublingual administration, containing 75,000 standardized quality tablet units of allergen extract of grass pollen (Phleum pratense). Grazax is indicated for treatment of grass pollen-induced rhinitis and conjunctivitis in adult and pediatric patients. Results from the GT-08 trial (first, second and third treatment years) showed a reduction of 31, 36 and 29%, respectively, in symptom scores and a reduction of 38, 45 and 40% of medication scores, respectively, compared with placebo. Subjects treated with Grazax also had an increased number of well days and a relevant improvement in quality of life. More subjects experienced excellent and complete rhinoconjunctivitis control in comparison with patients treated with symptomatic medications only. Grazax treatment is also associated with a sustained and relevant increase of specific IgG4. This increase is also observed after stopping AIT treatment. The most common adverse events related to Grazax treatment are local reactions, such as oral itch, edema of the mouth, ear pruritus, throat irritation and sneezing. Clinical efficacy of Grazax is observed also after 1 and 2 years of follow-up after stopping the AIT treatment. Grazax is efficacious and safe for treatment of grass-pollen rhinoconjunctivitis in both adults and children. Grazax is the first AIT showing a disease-modifying effect on grass pollen-induced allergic rhinoconjuctivitis.     

Onset of action of intranasal budesonide (Rhinocort aqua) in seasonal allergic rhinitis studied in a controlled exposure model

BACKGROUND: Intranasal budesonide aqueous nasal spray (BANS) is recognized as an efficacious treatment for seasonal allergic rhinitis (SAR), but the time to onset of action is not known. OBJECTIVE: The primary objective was to evaluate the time at which the onset of action of BANS in the symptomatic relief of seasonal allergic rhinitis becomes evident within 12 hours after a single dose in a controlled ragweed pollen exposure setting. METHODS: The study was of a double-blind, randomized, parallel-group design, testing BANS (64 microgram and 256 microgram) and placebo on ragweed-sensitive subjects with symptoms for at least 1 year by using a controlled pollen challenge system (Environmental Exposure Unit). The efficacy variables were the combined nasal score (the sum of blocked nose, runny nose, and sneezing-itchy nose), individual nasal symptoms, overall evaluation of treatment efficacy reported by participants on diaries, and peak nasal inspiratory flow (PNIF). RESULTS: A total of 217 participants were treated with BANS or placebo. At 7 to 12 hours, BANS was better than placebo in reducing combined nasal and blocked nose symptoms. For PNIF, the time to onset of action was shortest for 256 microgram of BANS relative to placebo (3 hours, P =.003). BANS 64 microgram was better than placebo in reducing the individual scores of blocked nose, runny nose, and sneezing-itchy nose from 3 to 5 hours after administration. Treatment efficacy was higher for those receiving BANS compared with placebo starting at 5 hours. All treatments were well tolerated, and no specific adverse events occurred. CONCLUSIONS: The onset of action of intranasal BANS was 7 hours according to combined nasal and blocked nose symptom scores. Evidence of earlier response was observed at 3 hours for runny nose and PNIF.     

Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy increases clinical efficacy

BACKGROUND: Sublingual immunotherapy treatment with grass allergen tablets (Grazax) is initiated preseasonally without up-dosing and treatment is continued throughout the entire grass pollen season. Aims of the study: The influence of the duration of preseasonal treatment on clinical efficacy obtained within the grass pollen season was investigated. METHODS: Data from three randomized, double-blind, placebo-controlled, multi-centre trials with varying preseasonal treatment periods were analysed. In the grass pollen season, symptom and medication score reductions relative to placebo were calculated and correlated with the duration of the preseasonal treatment period. RESULTS: The analysis was based on data from 934 patients. A significant reduction in seasonal daily rhinoconjunctivitis symptom and medication scores (17%, CI: 1-33% and 23%, CI: 1-47%, P < 0.05) was observed for patients treated with Grazax compared with placebo after approximately 8 weeks of pretreatment. The magnitude of the reductions in rhinoconjunctivitis symptom and medication scores increased with longer duration of preseasonal treatment (P < 0.0001). CONCLUSIONS: Sublingual immunotherapy with Grazax) must be initiated at least 8 weeks prior to the grass pollen season to provide a significant clinical efficacy. A longer preseasonal treatment period (>8 weeks) improves the clinical efficacy (relative to placebo) during the grass pollen season.     

Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis

BACKGROUND: Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. OBJECTIVE: To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis. METHODS: A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abelló, H?rsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. RESULTS: Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. CONCLUSION: This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. CLINICAL IMPLICATIONS: For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.     

Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid

BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.     

Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. METHODS: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. RESULTS: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.     

Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis

BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. OBJECTIVE: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, H?rsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. RESULTS: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.     

Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis.

BACKGROUND: Allergic patients often complain of eye symptoms during the allergy season. A possible mechanism for these eye symptoms is a nasal ocular reflex. OBJECTIVE: To demonstrate eye symptoms after nasal allergen challenge. METHODS: In a double-blind, placebo-controlled, crossover, clinical trial, 20 patients with seasonal allergic rhinitis were challenged in 1 nostril with antigen, and the response was monitored in both nostrils and in both eyes. Symptoms were recorded. Filter paper disks (intranasally) and Schirmer strips (intraocularly) were used for collecting secretions, which were subsequently eluted for the measurement of histamine and albumin levels. Patients were treated once topically at the site of challenge with azelastine or placebo. RESULTS: After placebo treatment, ipsilateral nasal challenge caused nasal symptoms and an increase in secretion weights; both were blocked by treatment with azelastine. Histamine and albumin levels increased only at the site of nasal challenge. Azelastine pretreatment inhibited the increase in albumin but not histamine levels. Symptoms of itchy and watery eyes increased significantly compared with symptoms with sham challenge after nasal allergen and were blocked by azelastine use. Ocular secretion weights increased bilaterally after placebo use and were not inhibited by azelastine use. CONCLUSIONS: Nasal allergen challenge releases histamine at the site of the challenge, which probably initiates a nasonasal and a nasal ocular reflex. This reflex is reduced by an H1-receptor antagonist applied at the site of the challenge. The eye symptoms associated with allergic rhinitis probably arise, in part, from a naso-ocular reflex.     

Efficacy of azelastine nasal spray in patients with an unsatisfactory response to loratadine.

OBJECTIVE: To evaluate the effectiveness and safety of azelastine nasal spray, desloratadine, and the combination of azelastine nasal spray plus loratadine compared with placebo in patients with seasonal allergic rhinitis who had an unsatisfactory response to loratadine. METHODS: This was a 2-week, multicenter, placebo-controlled, randomized, double-blind study in patients with moderate-to-severe symptoms of seasonal allergic rhinitis. Following a 1-week, open-label lead-in period, during which the patients received loratadine 10 mg daily, those patients who met the symptom qualification criteria (<25% to 33% improvement taking loratadine) were randomized to treatment with azelastine nasal spray 2 sprays per nostril, twice daily, azelastine nasal spray 2 sprays per nostril, twice daily, plus loratadine 10 mg daily, desloratadine 5 mg daily plus placebo (saline) nasal spray, or placebo (saline) nasal spray/placebo capsules. The primary efficacy variable was the change from baseline to day 14 in the total nasal symptom score, consisting of runny nose, sneezing, itchy nose, and nasal congestion symptom scores recorded twice daily (AM and PM) in patient diary cards. RESULTS: A total of 428 patients with an unsatisfactory response to loratadine completed the double-blind treatment period. After 2 weeks of treatment, azelastine nasal spray (P < 0.001), azelastine nasal spray plus loratadine (P < 0.001), and desloratadine (P = 0.039) significantly improved the total nasal symptom score compared with placebo. CONCLUSIONS: Azelastine nasal spray is an effective treatment for patients with seasonal allergic rhinitis who do not respond to loratadine and is an alternative to switching to another oral antihistamine or to using multiple antihistamines.     

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone. CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.     

Cost‐effectiveness of specific immunotherapy with Grazax in allergic rhinitis co‐existing with asthma

Background: In the United Kingdom, approximately 10.8 million people suffer from asthma, placing an economic burden on the society of more than £2 billion per year. For allergic asthma, treatment options consist of allergen avoidance, symptomatic treatment and allergen‐specific immunotherapy (SIT). Only SIT addresses the underlying cause of the disease, reducing symptoms and offering the potential for long‐term improvement. Grazax – the first tablet‐based SIT – is indicated for the treatment of patients with grass pollen‐induced rhinoconjunctivitis, including those with co‐existing asthma. Objective: To assess the cost‐effectiveness of Grazax in patients with rhinoconjunctivitis and co‐existing asthma. Methods: A prospective pharmacoeconomic analysis was carried out as part of a multinational clinical trial assessing the efficacy of Grazax (n = 79) compared with placebo (n = 72). Both groups had access to symptomatic medication; thus the placebo group represented current standard care. Pooled data on health resource use, productivity loss because of absence from work and quality of life (Quality Adjusted Life Years, QALYs) were collected in the trial. Reduced productivity at work was estimated from the literature. A societal perspective was adopted with a 9‐year time horizon. The NHS price of Grazax of £2.25 per tablet was used. Results: The QALY gain was significantly higher for patients treated with Grazax than the placebo group receiving symptomatic medication alone (0.197 discounted QALYs gained 9 years into the future – equal to an extra 72 days of perfect health over 9 years). The levels of resource use and productivity loss were higher for the placebo group. As a result, the cost per QALY gained with Grazax was £4319, which is highly cost‐effective. Price sensitivity analyses demonstrated that Grazax remained cost‐effective up to a tablet price of £5.07. Conclusion: SIT with Grazax is a cost‐effective strategy compared with standard management of patients with rhinoconjunctivitis and co‐existing asthma.     

A randomized comparison of the effects of budesonide and mometasone furoate aqueous nasal sprays on nasal peak flow rate and symptoms in perennial allergic rhinitis.

BACKGROUND: Using conventional methods, it has been difficult to show differences in efficacy between intranasal corticosteroids in perennial rhinitis. OBJECTIVE: To compare the effects of budesonide and mometasone on nasal symptoms and nasal airflow in perennial allergic rhinitis. METHODS: Four hundred thirty-eight patients (age > 18 years old) were randomized to budesonide, 256 microg or 128 microg, mometasone furoate 200 microg, or placebo, once daily for 4 weeks. Efficacy was evaluated by nasal index score (NIS; the sum of scores for blocked nose, runny nose, and itchy nose/sneezing) and peak nasal inspiratory flow (PNIF). RESULTS: All three active treatments significantly reduced the NIS compared with placebo. There was no significant difference between the treatments, although the effect of budesonide, 256 microg, tended to be greater than that of the other regimens. PNIF was significantly improved with all three active treatments: the effect of budesonide 256 microg on morning and evening PNIF was significantly greater than that of mometasone furoate and 128 microg budesonide. Budesonide had a rapid onset of action, showing a significantly greater effect on evening PNIF than mometasone furoate during the first 10 days. For all active treatments, significant improvements in NIS were seen within 4 hours of the first dose. All three treatments were well tolerated. CONCLUSION: The objective parameter PNIF was capable of demonstrating greater efficacy of budesonide 256 microg compared with budesonide 128 microg and mometasone furoate 200 microg, whereas the combined nasal symptom score could only distinguish active treatment from placebo.     

Efficacy of azelastine nasal spray in seasonal allergic rhinitis patients who remain symptomatic after treatment with fexofenadine.

BACKGROUND: Currently available oral second-generation antihistamines do not provide adequate symptom relief for many allergy patients. OBJECTIVE: To determine the ability of azelastine nasal spray to improve rhinitis symptoms in patients with seasonal allergic rhinitis who remained symptomatic after treatment with fexofenadine. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, 2-week study in patients with moderate-to-severe seasonal allergic rhinitis. The study began with a 1-week, open-label lead-in period, during which patients received fexofenadine, 60 mg twice daily. Patients who improved less than 25% to 33% with fexofenadine were randomized to treatment with (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) azelastine nasal spray, 2 sprays per nostril twice daily, plus fexofenadine, 60 mg twice daily; or (3) placebo (saline) nasal spray and placebo capsules twice daily. The primary efficacy variable was the change from baseline to day 14 in the total nasal symptom score (TNSS), consisting of runny nose, sneezing, itchy nose, and nasal congestion symptom scores. RESULTS: A total of 334 patients who remained symptomatic after treatment with fexofenadine were included in the efficacy analysis. After 2 weeks of treatment, azelastine nasal spray (P = .007) and azelastine nasal spray plus fexofenadine (P = .003) significantly improved the TNSS compared with placebo. Azelastine nasal spray monotherapy was as effective as the combination of azelastine nasal spray plus fexofenadine as measured by the TNSS and individual symptoms of the TNSS. CONCLUSIONS: Azelastine nasal spray is effective monotherapy for patients who remain symptomatic after treatment with fexofenadine and should be considered in the initial management of patients with seasonal allergic rhinitis.     

Fluticasone propionate aqueous nasal spray reduces inflammatory cells in unchallenged allergic nasal mucosa: effects of single allergen challenge

BACKGROUND: Topical corticosteroid therapy reduces symptoms and nasal mucosal inflammatory cells in patients with allergic rhinitis. Usually patients are advised to start their medication (1 week) before the beginning of the pollen season. The effect of pretreatment with a topical corticosteroid on unchallenged nasal mucosa is not well documented. OBJECTIVES: The purpose of this study was to investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks' pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms and inflammatory cell numbers after nasal allergen provocation in patients with seasonal allergic rhinitis. METHODS: Nineteen patients with grass pollen-induced allergic rhinitis were treated for a 6-week period out of the grass pollen season. After completing the treatment period, patients were challenged with grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient. In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils, macrophages, and Langerhans' cells were investigated. RESULTS: After 4 weeks of treatment but before allergen provocation, significantly fewer epithelial Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found in the fluticasone propionate group compared with those found in the placebo group. In the lamina propria significantly fewer Langerhans' cells and eosinophils were found in the fluticasone propionate group. Cell influx in nasal mucosa after allergen provocation was significantly inhibited in the fluticasone propionate group compared with that in the placebo group for epithelial Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria eosinophils, mast cells, Langerhans' cells, macrophages, and T cells. CONCLUSIONS: Fluticasone propionate is effective in reducing early- and late-phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory cells in unchallenged nasal mucosa.     

Effect of nasal anaesthesia on lacrimal function after nasal allergen challenge

Ocular symptoms in allergic rhinoconjunctivitis arise partly from direct contact of the allergen with the conjunctiva and presumably partly from a naso-lacrimal reflex. The aim was to study the importance of this reflex in allergic rhinitis after topical anaesthesia of the nose. Ten patients with allergic rhinoconjunctivitis lo birch pollen were challenged with increasing intranasal doses of allergen until allergic symptoms occurred. The same dose of allergen was used in two other provocations, when the nasal cavity was anaesthetized with topical lidocaine in a double-blind rundomized cross-over manner. The effect on the eyes was evaluated by Shirmer's test, a routine method for measuring tear production. Lidocaine per se and/or allergen challenge had no significant effect on tear production. The naso-lacrimal reflex was not involved in the eye symptoms, in allergic conjunctivitis.